Neonatal Cholestasis: Updates on Diagnostics, Therapeutics, and Prevention.

Cholestatic jaundice is a common presenting feature of hepatobiliary and/or metabolic dysfunction in the newborn and young infant. Timely detection of cholestasis, followed by rapid step-wise evaluation to determine the etiology, is crucial to identify those causes that are amenable to medical or surgical intervention and to optimize outcomes for all infants. In the past 2 decades, genetic etiologies have been elucidated for many cholestatic diseases, and next-generation sequencing, whole-exome sequencing, and whole-genome sequencing now allow for relatively rapid and cost-effective diagnosis of conditions not previously identifiable via standard blood tests and/or liver biopsy. Advances have also been made in our understanding of risk factors for parenteral nutrition-associated cholestasis/liver disease. New lipid emulsion formulations, coupled with preventive measures to decrease central line-associated bloodstream infections, have resulted in lower rates of cholestasis and liver disease in infants and children receiving long-term parental nutrition. Unfortunately, little progress has been made in determining the exact cause of biliary atresia. The median age at the time of the hepatoportoenterostomy procedure is still greater than 60 days; consequently, biliary atresia remains the primary indication for pediatric liver transplantation. Several emerging therapies may reduce the bile acid load to the liver and improve outcomes in some neonatal cholestatic disorders. The goal of this article is to review the etiologies, diagnostic algorithms, and current and future management strategies for infants with cholestasis.

Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: A pilot randomised placebo-controlled trial.

BACKGROUND: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257). METHODS: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events. FINDINGS: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment. INTERPRETATION: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome. FUNDING: Health Research Council of New Zealand, A Better Start - National Science Challenge.

Maternal and fetal outcomes in phaeochromocytoma and pregnancy: a multicentre retrospective cohort study and systematic review of literature.

BACKGROUND: Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. METHODS: We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression. FINDINGS: The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery). INTERPRETATION: Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. FUNDING: US National Institutes of Health.

Prevention of mother-to-child transmission activities after one-off clinical mentorship training in selected health facilities, Zimbabwe: 2014-2018.

This was a cross-sectional study describing HIV testing uptake and ART initiation for pregnant women and HIV-exposed infants after one-off clinical mentorship training in 2013 for nurses in 56 peripheral health-facilities, Zimbabwe. Between 2014-2018, 92% of 106411 pregnant women were HIV tested and 98% of HIV-positive women initiated antiretroviral therapy (ART). There were 15846 HIV-exposed infants, of whom 96% had dried blood spots collected for virologic diagnosis and 51% of those diagnosed HIV-positive initiated ART. In conclusion, this one-off clinical mentorship training in 2013 was associated with consistently high HIV testing and ART initiation in pregnant women and their children.

Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).

Sistema Rh-Hr y variantes del antígeno D en tres poblaciones afroecuatorianas del Valle del Chota / Rh-Hr system and D antigen variants in three Afro-Ecuadorian populations in the Chota Valley / Sistema Rh-Hr e variantes do antígeno D em três populações afro-equatorianas no vale do Chota

Resumen La identificación inequívoca del antígeno D en medicina transfusional es de vital importancia para evitar reacciones postransfusionales y la enfermedad hemolítica del recién nacido. Es común el uso de reactivos serológicos monoclonales o tarjetas de gel y su interpretación está definida por cruces, de acuerdo con la reacción serológica. El propósito de este estudio fue determinar la frecuencia del factor Rh y las variantes del antígeno D en una población afroecuatoriana. Se trató de un estudio descriptivo, transversal con muestreo aleatorio simple de 541 pobladores. Para la tipificación del factor Rh se utilizó la metodología en tubo con antisueros monoclonales y para la detección de las variantes de D se utilizaron tarjetas de gel IDCoombs Anti-IgG. Las lecturas se verificaron mediante el análisis del índice kappa. Se aplicó estadística descriptiva y el análisis de Chi cuadrado para establecer la relación de las variables y su significación. Se identificó una frecuencia del 92% de individuos Rh(D) positivo y un 8% Rh(D) negativo. El 4,80% de los individuos presentaban la variante D débil y el 79% reacciones serológicas entre 2 y 3(+) indicativas de otras variantes del antígeno D. El fenotipo más común fue el R0/R0. Estos datos demuestran la necesidad de confirmar la existencia de variantes del antígeno D en esta población para un mejor manejo de la sangre. Una limitante constituye la disponibilidad de técnicas moleculares para la genotipificación de D; sin embargo, se podría implementar la fenotipificación RHCE como estrategia pretransfusional.

Abstract The unequivocal identification of D antigen in transfusion medicine is of vital importance to avoid post-transfusion reactions and hemolytic disease of the newborn. The use of monoclonal serological reagents or gel cards is common and their interpretation is defined according to the serological reaction by crosses. The purpose of this study was to determine the frequency of Rh factor and D antigen variants in the Afro-Ecuadorian population. This was a descriptive, cross-sectional study with simple random sampling of 541 residents. Tube typing with monoclonal antisera was used to typify Rh factor and ID-Coombs Anti-IgG gel cards were used to detect D variants, and the readings were verified by analysis of the kappa index. Descriptive statistics and Chi-square analysis were applied for the relationship of the variables and their significance. A frequency of 92% of Rh(D) positive individuals and 8% Rh(D) negative individuals were identified. Almost 5% (4.80%) of the individuals presented the weak D variant and 79% serological reactions between 2-3(+) indicative of other D antigen variants, the most common phenotype being R0/R0. These data demonstrate the need to confirm the existence of D antigen variants in this population for better management and availability of blood. A limitation is the availability of molecular techniques for D genotyping, however, RHCE phenotyping could be implemented as a pretransfusion strategy.

Resumo A identificação inequívoca do antígeno D na medicina transfusional é de vital importância para evitar reações pós-transfusionais e a doença hemolítica do recém-nascido. É comum o uso de reagentes sorológicos monoclonais ou cartões de gel e sua interpretação é definida por cruzamentos de acordo com a reação sorológica. O objetivo deste estudo foi determinar a frequência do fator Rh e as variantes do antígeno D numa população afro-equatoriana. Foi um estudo descritivo, transversal, com amostragem aleatória simples de 541 residentes. Para a tipagem do fator Rh foi utilizada a metodologia em tubo com anti-soros monoclonais e para a detecção das variantes de D, os cartões de gel ID-Coombs Anti-IgG. As leituras foram verificadas por análise do índice kappa. Foi aplicada estatística descritiva e para estabelecer a relação das variáveis e sua significação se utilizou a análise do qui-quadrado. Identificando uma frequência de 92% dos indivíduos Rh (D) positivos e 8% Rh (D) negativos. 4,80% dos indivíduos apresentavam a variante D fraca e 79% reações sorológicas entre 2 e 3(+) indicativas de outras variantes do antígeno D, sendo o fenótipo mais comum o R0/R0. Esses dados demonstram a necessidade de confirmar a existência de variantes do antígeno D nessa população para melhor gerenciamento e disponibilidade de sangue. Uma limitação é a disponibilidade de técnicas moleculares para a genotipagem de D, no entanto, a fenotipagem de RHCE poderia ser implementada como uma estratégia de pré-transfusão.

Tuberculosis in pregnant women and neonates: A meta-review of current evidence.

Pregnant women and their infants are a vulnerable but neglected population in tuberculosis (TB) control efforts. Recent advances in TB prevention, diagnosis and treatment have implications for their care, despite their frequent exclusion from research. We have conducted a meta-review of current evidence and clinical guidelines for TB prevention, diagnosis and management in pregnant women and neonates, focusing on review articles published since 2010. The actual burden of TB in pregnancy is unmeasured, but has been estimated at 216,500 cases per year. Although the effect of pregnancy on TB risk is uncertain and controversial, two large whole-of-population studies found that pregnancy was associated with a two- to three-fold increase in risk of TB. Congenital TB is rare but extremely serious. Neonates exposed to TB after delivery will be at high risk of disease, and preventive therapy is recommended once disease has been ruled out. At present, there is limited evidence regarding the performance of different screening strategies for pregnant women, appropriate drug dosing for either pregnant women or neonates, and the safety of most second-line drugs in pregnancy. High quality evidence on these topics is needed, as are detailed guidelines to inform efforts by TB control programs and clinicians working with pregnant women and their infants.

Stem cell therapy for preventing neonatal diseases in the 21st century: Current understanding and challenges.

Diseases of the preterm newborn such as bronchopulmonary dysplasia, necrotizing enterocolitis, cerebral palsy, and hypoxic-ischemic encephalopathy continue to be major causes of infant mortality and long-term morbidity. Effective therapies for the prevention or treatment for these conditions are still lacking as recent clinical trials have shown modest or no benefit. Stem cell therapy is rapidly emerging as a novel therapeutic tool for several neonatal diseases with encouraging pre-clinical results that hold promise for clinical translation. However, there are a number of unanswered questions and facets to the development of stem cell therapy as a clinical intervention. There is much work to be done to fully elucidate the mechanisms by which stem cell therapy is effective (e.g., anti-inflammatory versus pro-angiogenic), identifying important paracrine mediators, and determining the timing and type of therapy (e.g., cellular versus secretomes), as well as patient characteristics that are ideal. Importantly, the interaction between stem cell therapy and current, standard-of-care interventions is nearly completely unknown. In this review, we will focus predominantly on the use of mesenchymal stromal cells for neonatal diseases, highlighting the promises and challenges in clinical translation towards preventing neonatal diseases in the 21st century.

Continuous vital sign analysis for predicting and preventing neonatal diseases in the twenty-first century: big data to the forefront.

In the neonatal intensive care unit (NICU), heart rate, respiratory rate, and oxygen saturation are vital signs (VS) that are continuously monitored in infants, while blood pressure is often monitored continuously immediately after birth, or during critical illness. Although changes in VS can reflect infant physiology or circadian rhythms, persistent deviations in absolute values or complex changes in variability can indicate acute or chronic pathology. Recent studies demonstrate that analysis of continuous VS trends can predict sepsis, necrotizing enterocolitis, brain injury, bronchopulmonary dysplasia, cardiorespiratory decompensation, and mortality. Subtle changes in continuous VS patterns may not be discerned even by experienced clinicians reviewing spot VS data or VS trends captured in the monitor. In contrast, objective analysis of continuous VS data can improve neonatal outcomes by allowing heightened vigilance or preemptive interventions. In this review, we provide an overview of the studies that have used continuous analysis of single or multiple VS, their interactions, and combined VS and clinical analytic tools, to predict or detect neonatal pathophysiology. We make the case that big-data analytics are promising, and with continued improvements, can become a powerful tool to mitigate neonatal diseases in the twenty-first century.

17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial.

BACKGROUND: Women with a history of spontaneous preterm birth (SPTB) are at a significantly increased risk for recurrent preterm birth (PTB). To date, only one large U.S. clinical trial comparing 17-OHPC (17-α-hydroxyprogesterone caproate or "17P") to placebo has been published, and this trial was stopped early due to a large treatment benefit. OBJECTIVE: This study aimed to assess whether 17-OHPC decreases recurrent PTB and neonatal morbidity in women with a prior SPTB in a singleton gestation. STUDY DESIGN: This was a double-blind, placebo-controlled international trial involving women with a previous singleton SPTB (clinicaltrials.gov: NCT01004029). Women were enrolled at 93 clinical centers (41 in the United States and 52 outside the United States) between 160/7 to 206/7 weeks in a 2:1 ratio, to receive either weekly intramuscular (IM) injections of 250 mg of 17-OHPC or an inert oil placebo; treatment was continued until delivery or 36 weeks. Co-primary outcomes were PTB < 35 weeks and a neonatal morbidity composite index. The composite included any of the following: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, or proven sepsis. A planned sample size of 1,707 patients was estimated to provide 98% power to detect a 30% reduction in PTB < 35 weeks (30% to 21%) and 90% power to detect a 35% reduction in neonatal composite index (17%-11%) using a two-sided type-I error of 5%. Finally, this sample size would also provide 82.8% power to rule out a doubling in the risk of fetal/early infant death assuming a 4% fetal/early infant death rate. Analysis was performed according to the intention-to-treat principle. RESULTS: Baseline characteristics between the 1,130 women who received 17-OHPC and 578 women who received placebo were similar. Overall, 87% of enrolled women were Caucasian, 12% had >1 prior SPTB, 7% smoked cigarettes, and 89% were married/lived with partner. Prior to receiving study drug, 73% women had a transvaginal cervical length measurement performed and <2% had cervical shortening <25 mm. There were no significant differences in the frequency of PTB < 35 weeks (17-OHPC 11.0% vs. placebo 11.5%; relative risk = 0.95 [95% confidence interval (CI): 0.71-1.26]) or neonatal morbidity index (17-OHPC 5.6% vs. placebo 5.0%; relative risk = 1.12 [95% CI: 0.68-1.61]). There were also no differences in frequency of fetal/early infant death (17-OHPC 1.7% vs. placebo 1.9%; relative risk = 0.87 [95% CI: 0.4-1.81]. Maternal outcomes were also similar. In the subgroup of women enrolled in the United States (n = 391; 23% of all patients), although the rate of PTB < 35 weeks was higher than the overall study population, there were no statistically significant differences between groups (15.6% vs. 17.6%; relative risk = 0.88 [95% CI: 0.55, 1.40]. CONCLUSION: In this study population, 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death.

The Association of Concomitant Maternal Marijuana Use on Health Outcomes for Opioid Exposed Newborns in Massachusetts, 2003-2009.

This population-based study showed that maternal opioid plus marijuana use during pregnancy was associated with increased odds of prematurity and low birth weight but lower odds of neonatal abstinence syndrome and prolonged hospitalization compared with opioid exposure without marijuana use. Further research should evaluate the biologic mechanisms responsible for these outcomes.

Aspectos clínico-epidemiológicos de las infecciones de piel y partes blandas en neonatos / Clinical-epidemiological aspects of skin and soft tissue infections in newborns

Introducción: Las infecciones de piel y partes blandas constituyen una de las causas más frecuentes de consulta pediátrica, de lo cual no está exento el recién nacido, que por sus peculiaridades anatómicas, fisiológicas e inmunológicas, pueden convertirse en afecciones letales. Objetivo: Describir aspectos clínicos y epidemiológicos de los recién nacidos con infecciones de piel y partes blandas. Métodos: Se realizó un estudio observacional, prospectivo y transversal en 256 pacientes que ingresaron en el Departamento de Neonatología del Hospital Pediátrico Universitario William Soler de enero de 2013 a diciembre de 2015. Se determinó la incidencia de las infecciones de piel y partes blandas, formas clínicas de presentación, edad, sexo, estadía, terapéutica utilizada y microorganismos aislados en hemocultivo. Resultados: En la muestra, 95,3 por ciento de los neonatos tenían más de 7 días de nacidos y 59,0 por ciento eran hembras. La tasa de incidencia fue de 16,1 × 100 ingresos y el 75,0 por ciento presentaba mastitis. El microorganismo más aislado en hemocultivos fue Staphylococcus aureus. El 60,9 por ciento de los pacientes recibieron monoterapia con Cefazolina. Conclusiones: La incidencia de las infecciones de piel y partes blandas fue mayor en el año 2014; los recién nacidos inician la enfermedad en la segunda semana de vida, en el sexo femenino, con una estadía hospitalaria menor de una semana. El microorganismo más aislado en hemocultivos es Staphylococcus aureus. Más de la mitad de los pacientes reciben monoterapia con Cefalosporina de primera generación como terapéutica con una evolución favorable(AU)

Introduction: Skin and soft tissue infections constitute one of the most frequent causes of pediatric consultations. Newborns are not exempt of that since their anatomic, physiological and immunological peculiarities can help to become those infections in letal ones. Objective: To describe clinical and epidemiological aspects of newborns presenting skin and soft tissue infections. Methods: An observational, prospective and cross-sectional study was carried out in 256 patients admitted in the Neonatology Department of William Soler Pediatric University Hospital from January, 2013 to Decmeber, 2015. There were determined: the incidence of skin and soft tissue infections, the clinical kinds, age, sex, stay, used therapy, microorganisms isolated in hemocultures. Results: In the sample, 95.3 percent of the newborns were of more than 7 days alive and 59.0 percent were female. The incidence rate was of 16.1 × 100 admissions, and 75.0 percent presented mastitis. The most isolated in hemocultures microorganism was Staphylococcus aureus. 60.9 percent of the patients had monotherapy with Cefazolin. Conclusions: The incidence of skin and soft tissue infections was higher in 2014; the disease onset in newborns in the second week of life, in females, with a hospital stay of less than a week. The most isolated in hemocultures microorganism is Staphylococcus aureus. More tan half of the patients undergone monotherapy with first generation Cephalosporines as a therapy with a favorable evolution(AU)

Hyperthyroidism and Pregnancy.

Clinical hyperthyroidism affects 0.1% to 0.4% of pregnancies. Gestational thyrotoxicosis is due to homology of the structure of TSH and HCG, which weakly stimulates the TSH receptor. Graves' disease (GD) most commonly causes clinically significant hyperthyroidism. Given concerns for teratogenicity from antithyroid drugs, these may be discontinued in low-risk GD patients. High-risk patients are treated with propylthiouracil in the first trimester then may transition to methimazole. Surgery is reserved for special circumstances; radioactive iodine is contraindicated. In late pregnancy, GD may remit; postpartum relapse is common. Measurement of serum thyrotropin receptor antibodies identifies pregnancies at-risk for fetal and neonatal hyperthyroidism.

Análisis microbiológico del tracto genital materno y de la sangre del cordón umbilical en relación con el daño neonatal / Microbiological analysis of the maternal genital tract and umbilical cord blood and its association with neonatal damage

La etiología que conduce al daño neonatal es multifactorial, y los procesos infecciosos pueden estar implicados en él. El objetivo de este estudio fue identificar microorganismos del tracto genital materno asociados con el daño neonatal, a fin de prevenir futuras complicaciones perinatológicas. Se estudiaron 711 embarazadas que concurrieron entre enero de 2010 y julio 2013 al consultorio externo de Obstetricia del Hospital de Clínicas de la UBA para sus controles prenatales, y cuyos partos también tuvieron lugar en dicho nosocomio. En la sangre del cordón umbilical se investigó la presencia de Ureaplasma urealyticum y Mycoplasma hominis mediante el cultivo con sustratos metabólicos (Micofast-Biomerieux), y la de Trichomonas vaginalis por PCR, con primers específicos. El estudio microbiológico del contenido vaginal se efectuó en 288 de las embarazadas en la semana 35 a 37. Se empleó la metodología convencional, a la que se agregó el cultivo en tioglicolato modificado para T. vaginalis. Se investigó la presencia de estreptococos grupo B (EGB) en hisopado anorrectaly de introito vaginal, utilizando enriquecimiento en caldo selectivo y posterior siembra en medio cromogénico. Se utilizaron los test de χ² Yates y de Fisher para muestras independientes, considerándose significativo p < 0,05. La vaginosis bacteriana (VB) se relacionó significativamente con el daño neonatal (p = 0,02), al igual que la presencia de M. hominis (p = 0,03) y de T. vaginalis (p = 0,03) en la sangre del cordón umbilical. Las complicaciones predominantes fueron el parto pretérmino, la rotura prematura de membrana (RPM), el bajo peso y un valor de Apgar <7. No se asoció al daño neonatal la presencia de U. urealyticum (p = 0,35) en el cordón umbilical, ni la de Candidaspp. (p = 0,94) o EGB (p = 0,18) en el tracto genital de las madres. Dado que ciertas alteraciones en la microbiota del tracto genital materno se relacionaron con el dano neonatal, consideramos de fundamental importancia realizar el estudio microbiológico del contenido vaginal durante el embarazo, para prevenir posibles complicaciones maternas y perinatológicas.

The etiology leading to neonatal damage is multifactorial, being genital infections one of the causes. The objective of the study was to identify microorganisms of the maternal genital tract that are associated with neonatal damage, in order to prevent future perinatal complications. Seven hundred and eleven pregnant patients attended their prenatal control during the period January 2010-July 2013. Ureaplasma urealyticum and Mycoplasma hominis presence was investigated in umbilical cord blood by metabolic substrates (Micofast-Biomerieux) and that of T. vaginalis, by PCR using specific primers. The microbiological study of the vaginal contents of 288 pregnant patients at weeks 35 to 37 was performed by conventional methods, adding the modified thioglycolate culture for T. vaginalis. Group B streptococcus (GBS) was investigated in anorectal and vaginal introitus swabs, using selective broth enrichment and subsequent isolation in chromogenic medium. The χ² Yates test and Fisher's test were used for independent samples. A p value <0.05 was considered statistically significant. The pathogens significantly related to neonatal damage were M. hominis (p = 0.03), T. vaginalis (p = 0.03), and BV (p = 0.02). Main complications were preterm birth, premature rupture of membranes (PRM), low weight and Apgar score <7. U. urealyticum (p = 0.35), Candidaspp. (p = 0.94) and GBS (p = 0.18) were not related to neonatal damage. Since different microorganisms of the maternal genital tract were related to neonatal damage, it is very important to perform the microbiological study of vaginal contents during pregnancy to prevent possible maternal and perinatal complications.

Vitamin D Deficiency, Prevalence and Treatment in Neonatal Period.

OBJECTIVE: Maternal vitamin D deficiency is an important risk factor that causes infantile rickets in the neonatal and infantile period. The aim of this study was to review the prevalence, clinical characteristics, and treatment of vitamin D deficiency and the follow-ups with infants and their mothers by the neonatal intensive care unit of Afiyet Hospital in Turkey. METHODS: Calcium (Ca), phosphorus (P) and 25 (OH) vitamin D were studied and prospectively recorded in infants and their mothers detected to have hypocalcemia during routine biochemistry tests performed on the third postnatal day of the patients follow up and treated with different diagnoses. RESULTS: A total of 2,460 infants were admitted into the neonatal intensive care unit between August 2014 and January 2018. Of the infants included in the study, 324 (66.1%) were male and 166 (33.8%) were female, and 366 (74.6%) of them had been delivered by cesarean section (C/S), 124 (25.3%) of them had been delivered by Normal Spontaneous Delivery (NSD). Hypocalcemia was detected in 490 (19.9%) of the infants. In a total of 190 (38.7%) infants and 86 mothers (17.5%), the levels of 25 (OH) vitamin D were found to be below the laboratory detection limit of <3 ng/ml. When vitamin D deficiency + insufficiency is assessed by season, 151 of them were found to be in summer (30.99%), 118 in spring (24.18%), 117 in the winter season(23.87%), and 93 in autumn(18.97%), respectively. There was a statistically significant positive correlation of 78.7% between the vitamins D values of the mothers and the infants (p: 0.000, p<0.05). CONCLUSION: This study conducted that a positive correlation of between the vitamin D values of the mothers and the infants. In order to prevent maternal vitamin D deficiency, the appropriate dose of prophylaxis providing optimal levels of vitamin D and should be given by according to the levels of 25 (OH) D vitamin during pregnancy.

Effect of Early Parenteral Nutrition Discontinuation on Time to Regain Birth Weight in Very Low Birth Weight Infants: A Randomized Controlled Trial.

BACKGROUND: Peripherally inserted central catheters (PICCs) are used to administer parenteral nutrition (PN) in very low birth weight infants (VLBW; <1500 g). Clinicians try to optimize early nutrition but also minimize the risks associated with intravascular devices. The objective of this study was to examine the early nutrition impact of discontinuing PN at different enteral feed volumes in VLBW infants. METHODS: In this unmasked, multicenter, randomized controlled trial, patients were randomly assigned to PICC removal and PN discontinuation at an enteral feed volume of 100 mL/kg/day (intervention) or 140 mL/kg/day (control). Clinically stable VLBW infants with a PICC in situ who were receiving PN were eligible for inclusion. Infants with major congenital anomalies were excluded. A total of 139 patients were enrolled; 69 and 70 patients were randomized to the intervention and control groups, respectively. The primary outcome measure was the mean difference in time (days) to regain birth weight. RESULTS: The groups were well matched at study entry. Patients in the intervention group regained birth weight more slowly (mean difference 1.5 days CI: 0.3-2.7 days, P = 0.01). The mean difference in time to regain birth weight for infants <1000 g was 2.8 days (95% CI: 0.8-4.8 days, P = 0.008). CONCLUSIONS: In VLBW infants, early PICC removal at an enteral feed volume of 100 mL/kg/day compared with later removal at 140 mL/kg/day resulted in a significant delay in time to regain birth weight, and this delay was more pronounced in infants <1000 g.

How does preeclampsia affect neonates? Highlights in the disease's immunity.

INTRODUCTION: Preeclampsia (PE) is the primary obstetrical cause in one of the four perinatal deaths. Although the etiology and pathogenesis of preeclampsia is not fully known, a proinflammatory immune state prevails and can disrupt fetal hematopoiesis. Some of the effects on the newborn include neonatal thrombocytopenia, neutropenia, a reduction in T regulatory cells, and an increased cytotoxic natural killer cell profile. METHODS: Electronic databases were searched, and defined criteria were applied to select articles for review. The review covered literature on the effects on neonatal due to maternal preeclampsia, fetal outcomes, and new treatments in research aimed at reducing morbidity and mortality of the disease. DISCUSSION: The cytotoxic environment present in PE affects the development of fetal cell lineages. Neutropenia is observed in 50% of neonates and is correlated with mortality, although its treatment is not well-established. The enhancement in erythropoietin and the hypoxic setting present in the disease can also lead to thrombocytopenia. Per partum management includes platelet transfusion in order to avoid severe complications such as intraventricular hemorrhage. Regarding other cell lines, a cytotoxic profile is observed to be reflecting the milieu present in the mothers' bloodstream. This disruption alters the immune system response into a proinflammatory profile and can be correlated to neonatal necrotizing enterocolitis. An antiangiogenic environment is also part of the preeclampsia presentation and can be responsible for the enhancement of bronchopulmonary dysplasia observed in this population. Meanwhile, the reduction in angiogenic factors, such as vascular endothelial growth factor (VEGF), can be a protective mechanism for retinopathy of prematurity. Studies of the long-term effects of these observations are lacking, but lower neurodevelopmental scores and a higher cardiovascular risk are noted. New treatments in research propose a prevention of the disease during gestation in order to reduce the effects more efficiently in the fetus. Phosphodiesterase inhibitors, endothelin 1 receptor antagonists and manipulation of heme oxygenase-1 enzyme pathway are possible therapeutic alternatives. This review summarizes the current understanding of how preeclampsia affects neonates. As a conclusion, further studies are needed to build up a guideline to manage those effects. A research agenda is proposed.

Donor human milk and risk of surgical necrotizing enterocolitis: A meta-analysis.

BACKGROUND & AIM: The prevention of necrotizing enterocolitis (NEC) is a primary goal in the care of preterm and low birth-weight infants. Donor-banked milk (DM)-feeding has been reported to have a protective effect towards NEC with respect to formula-feeding. All the meta-analysis published so far, have been focused on the protective effect of DM on the overall risk of NEC, none of them focused on the risk of the most severe cases on NEC only, that are those requiring surgery. We conducted a meta-analysis of available evidences on the risk of developing surgical cases of NEC in DM-fed preterm and/or low birth weight infants with respect to those formula-fed. METHODS: A search for articles published between January 1960 and January 2018 and addressing the association between DM and surgical NEC was conducted via PubMed, Embase and Cochrane database. We included randomized controlled clinical trials, reporting primary data and involving preterm and/or low birth weight infants fed with preterm formula compared to DM, both as sole diet or complementing own mother's milk. Estimates were pooled using random-effects. Study quality was assessed by GRADE score and risk of bias by the Review Manager software tool. RESULTS: Four papers were included in the meta-analysis. DM did not exert a beneficial effect of DM on the risk of preventing surgical NEC with respect to formula (RR: 0.45; 95% CI: 0.19-1.09). CONCLUSIONS: This meta-analysis indicates that DM does not exert a clear protective effect, on the surgical cases of NEC with respect to preterm formula. Since DM feeding implies remarkable extra cost for the preparation, storage and delivery of the milk with respect to preterm formula, stronger evidences are required to recommend this type of feeding as a preventive strategy for surgical NEC. Mother's milk, when available, could represents the best choice. PROSPERO REGISTRATION NUMBER: CRD42015020296.